Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer

Phase 2

• Conditions: Endometrium Cancer; Uterine Neoplasms; Endometrial Neoplasms
• Interventions: Drug: PARP inhibitor and Anti-PD-L1

• Registration Number: NCT03951415
• Lead Sponsor: Leiden University Medical Center

Brief Summary

The DOMEC trial is designed as a Dutch Gynecological Oncology Group (DGOG), prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer or carcinosarcoma of the uterus to investigate the efficacy of the combination therapy of olaparib tablets and durvalumab IV.

Detailed Description

The prognosis of recurrent or persistent endometrial carcinoma not amenable to local therapy is poor. First line therapy exists of platinum-based chemotherapy or hormonal therapy. No standard subsequent-line therapy has been described.The combination of Poly(ADP-ribose) polymerases (PARP) inhibition and Programmed death-ligand 1 (PD-L1) blocking has great potential in the treatment of recurrent endometrial cancer. The DOMEC trial is designed to investigate this treatment combination among all molecular subgroups.

The DOMEC trial is designed as a DGOG, prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer, including carcinosarcoma of the uterus. Patients must have had one prior platinum-based chemotherapeutic regimen or not be able/willing to get chemotherapy. The aim is to investigate the efficacy of the combination therapy of olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks in terms of progression free survival. Secondary objectives are to investigate objective response rate, overall survival, safety and predictive biomarkers.

Study Timeline

• Study First Submitted: 2019-04-30
• Study First Submitted QC: 2019-05-14
• Study First Posted: 2019-05-15
• Study Start: 2019-07-08
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-30
• Last Update Posted: 2021-04-01
• Primary Completion: 2021-08-01
• Study Completion: 2021-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 55

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PARP inhibitor and Anti-PD-L1	PARP inhibitor and Anti-PD-L1	olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	6 months	PFS will be counted from the date of registration until the first observation of radiological progressive disease according to RECIST 1.1 criteria or death due to any cause, whichever occurred first.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Through study completion, up to 36 months	OS will be determined from the date of registration until death from any cause.
Adverse events	Through study completion, up to 36 months	Assessed by NCI Common Terminology Criteria for adverse Events (CTCAE) version 5.0
Predictive biomarkers in tumor biopsy	At baseline	MMRd/POLE, HR status, quantification of CD3,CD4,CD8,CD103,CD161,PD-1,LAG3,CTLA-4,NKG2A,GOXp3 positieve T cells, NK cells, percentage PD-L1 on myeloid cells/tumorcells, quantification of myeloid cell infiltration (CD68,CD14,CD33,CD163) in tumor biopsies.
Objective response rate (ORR)	12 weeks	according to RECIST 1.1 criteria

Trial Locations

Locations (8)

Amsterdam UMC, AMC; 🇳🇱 Amsterdam, Netherlands

NKI-AVL; 🇳🇱 Amsterdam, Netherlands

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Academisch Ziekenhuis Maastricht; 🇳🇱 Maastricht, Netherlands

RadboudMC; 🇳🇱 Nijmegen, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands